Three researchers at Karolinska Institutet are being awarded prestigious grants from the European Research Council (ERC). Jens Hjerling Leffler, Anna Rising and Maja Jagodic each receive the ERC Consolidator Grant 2018 for research on, respectively, brain cell type-specific interactions in schizophrenia; the generation of artificial spider-silk super fibers; and epigenetics in multiple sclerosis.

This funding programme awards up to EUR 2 million per project over a five year period, and is aimed at mid-career researchers who have recently started their own group and strive to strengthen their role as research leaders. Awarded researchers and projects at KI in 2018:

Summary: Schizophrenia is a devastating psychiatric disorder that is caused by many minor disturbances or variations in the regulation of hundreds of genes. This makes it difficult to understand where in the brain the most important errors occur, and if malfunctions in one type of cells can also cause pathological changes in adjacent cells. In the project now funded by the ERC, Dr. Jens Hjerling Leffler and his colleagues will investigate a new way of measuring the overall impact of the many minor genetic variations in specific cells, in both mice and humans. The researchers will then recreate this overall impact in only one type of brain cell in an otherwise healthy mouse, in order to be able to systematically investigate how disease-related changes in one cell can affect the function of nearby cells. Increased knowledge on how, when and where genetic changes lead to schizophrenia could hopefully contribute to the development of new therapies that can be used earlier in the disease process – or perhaps even before disease onset.

Summary: Spider silk is nature’s high performance material and has the potential to be used as a biomaterial for medical applications. However, production and spinning of artificial spider silk fibers are very challenging, and current methods to produce silk fibers include conditions which prevent the silk proteins from assembling into fibers in the same complex way that native silk proteins do. Recently, Dr. Anna Rising and her colleagues succeeded in spinning biomimetic spider silk using the same mild conditions as the spider does. In the project now funded by the ERC, the researchers will build further on these technical leaps – aiming to generate artificial silk fibers that are equal or superior to native spider silk in terms of toughness and tensile strength. To reach this goal, they will use genetic information and protein engineering to design new silk proteins, and decipher the relationships between protein structure and mechanical properties of the fibers. This information will be important not only for the generation of strong fibers, but also for the basic understanding of protein fibrillation in, for example, Alzheimer’s disease.

Project: Epi4MS – targeting the epigenome for a better understanding of disease pathogenesis and novel therapeutic strategies in Multiple Sclerosis

Summary: Multiple Sclerosis (MS) is a leading cause of incurable progressive disability in young adults. The Epi4MS project aims to identify epigenetic causes of MS and to develop novel therapeutic strategies based on inducing self-sustained reversal of aberrant epigenetic states. Dr. Maja Jagodic and her colleagues will utilize unique MS biomaterial combined with cutting-edge methodologies to capture relevant cells and measure their functional states. The impact of MS-associated changes will be evaluated using innovative in vitro epigenome screens. The researchers will then utilize animal models to dissect the molecular mechanisms of MS-associated changes in vivo and test the therapeutic potential of targeted epigenome-editing. Epi4MS aims at a paradigm-shift in studying and treating complex inflammatory diseases.